基于网络药理学、分子对接和分子动力学模拟探讨虎杖苷防治脊髓缺血再灌注损伤的作用机制。
Mechanisms of polydatin against spinal cord ischemia-reperfusion injury based on network pharmacology, molecular docking and molecular dynamics simulation.
机构信息
Department of Spinal Surgery, Xiangya Hospital of Central South University, Changsha, PR China.
School of Life Science and Technology, Central South University of Forestry and Technology, Changsha, PR China.
出版信息
Bioorg Chem. 2023 Nov;140:106840. doi: 10.1016/j.bioorg.2023.106840. Epub 2023 Sep 8.
BACKGROUND
Polydatin has shown considerable pharmacological activities in ischemia-reperfusion injuries of various organs. However, its effects and mechanisms in spinal cord ischemia-reperfusion injury have not been fully established. In this study, the mechanisms of polydatin against spinal cord ischemia-reperfusion injury were investigated via network pharmacology, molecular docking and molecular dynamics simulation.
METHODS
Spinal cord ischemia-reperfusion injury-related targets were obtained from the GeneCards database, while polydatin-related action targets were obtained from the CTD and SwissTarget databases. A protein-protein interaction network of potential targets was constructed using the String platform. After selecting the potential key targets, GO functional enrichment and KEGG pathway enrichment analyses were performed via the Metascape database, and a network map of "drug-target-pathway-disease" constructed. The relationships between polydatin and various key targets were assessed via molecular docking. Molecular dynamics simulation was conducted for optimal core protein-compound complexes obtained by molecular docking.
RESULTS
Topological analysis of the PPI network revealed 14 core targets. GO functional enrichment analysis revealed that 435 biological processes, 12 cell components and 29 molecular functions were enriched while KEGG pathway enrichment analysis revealed 91 enriched signaling pathways. Molecular docking showed that polydatin had the highest binding affinity for MAPK3, suggesting that MAPK3 is a key target of polydatin against spinal cord ischemia-reperfusion injury. Molecular dynamics simulations revealed good binding abilities between polydatin and MAPK3.
CONCLUSIONS
Polydatin exerts its effects on spinal cord ischemia-reperfusion injury through multiple targets and pathways. MAPK3 may be a key target of polydatin in spinal cord ischemia-reperfusion injury.
背景
白藜芦醇苷在多种器官的缺血再灌注损伤中显示出相当大的药理活性。然而，其在脊髓缺血再灌注损伤中的作用和机制尚未完全确定。在这项研究中，通过网络药理学、分子对接和分子动力学模拟研究了白藜芦醇苷对脊髓缺血再灌注损伤的作用机制。
方法
从 GeneCards 数据库中获得与脊髓缺血再灌注损伤相关的靶点，从 CTD 和 SwissTarget 数据库中获得白藜芦醇苷相关作用靶点。使用 String 平台构建潜在靶点的蛋白质-蛋白质相互作用网络。选择潜在关键靶点后，通过 Metascape 数据库进行 GO 功能富集和 KEGG 通路富集分析，并构建“药物-靶点-通路-疾病”网络图谱。通过分子对接评估白藜芦醇苷与各种关键靶点的关系。对分子对接得到的最优核心蛋白-化合物复合物进行分子动力学模拟。
结果
PPI 网络的拓扑分析显示出 14 个核心靶点。GO 功能富集分析显示，435 个生物过程、12 个细胞成分和 29 个分子功能被富集，KEGG 通路富集分析显示 91 个信号通路被富集。分子对接显示，白藜芦醇苷与 MAPK3 的结合亲和力最高，提示 MAPK3 是白藜芦醇苷治疗脊髓缺血再灌注损伤的关键靶点。分子动力学模拟显示白藜芦醇苷与 MAPK3 之间具有良好的结合能力。
结论
白藜芦醇苷通过多个靶点和通路发挥对脊髓缺血再灌注损伤的作用。MAPK3 可能是白藜芦醇苷治疗脊髓缺血再灌注损伤的关键靶点。
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